Abstract:

Background and Objectives
The advent of Highly Active Antiretroviral Therapy (HAART) has resulted in a significant reduction in HIV/AIDS related morbidity and mortality in sub-Saharan Africa. However, toxicities due to HAART continue to pose challenges to the success of different regimens. Severe hepatotoxicity is one of the significant adverse events occurring in patients on HAART. Information on the incidence and risk factors for severe hepatotoxicity in cohorts from resource poor settings is limited. It is against this background that we undertook the study to determine the incidence and explore factors associated with severe hepatotoxicity following HAART initiation in a South African cohort.
Materials and Methods
Secondary data analysis of a prospective cohort 9764 HIV-infected adult patients initiated on HAART at the Themba Lethu clinic antiretroviral rollout facility in Johannesburg, South Africa between 1st April 2004 and 30th June 2009 was conducted. Severe hepatotoxicity cases were identified within the first 12 months of initiating HAART as grade 3 or 4 elevation in baseline ALT levels. The incidence rate of severe hepatotoxicity was calculated and potential socio-demographic and clinical predictors were explored using Cox proportional hazard regression modelling.
Results
At baseline, 91.8% of patients were commenced on an efavirenz-based regimen while only 8.2% were on a nevirapine-based regimen. The median CD4 count at
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initiation of HAART for this cohort was 80 cells/ mm3, a figure lower than the Department of Health (DoH) CD4 cut off for initiating HAART of 200 cells/ mm3.
The overall incidence rate of severe hepatotoxicity was 10.7 (95% CI: 8.7 – 13.1) cases per 1000 p-yrs of follow-up. The period with the highest risk of severe hepatotoxicity was within 2 months of initiating HAART. Incidence of severe hepatotoxicity was 21.1(95% CI: 12.7 – 34.9) cases per 1000 p-yrs among patients on a nevirapine-based regimen and 9.7 (95% CI: 7.8 – 12.1) cases per 1000 p-yrs in those on an efavirenz-based one.
The hazard for severe hepatotoxicity within the first year of initiating HAART was 2.17 times higher in individuals on a nevirapine-based regimen compared to those on an efavirenz-based regimen after adjusting for baseline ALT, baseline CD4, age and gender (HR = 2.17; 95%CI = 1.18 – 3.97; p = 0.013). Though imprecise, the estimate for baseline ALT category suggested an increased risk for severe hepatotoxicity in individuals with a baseline ALT more than 40 I.U/L compared to those with a baseline ALT of less than 40 I.U/L (HR = 1.63; 95%CI = 1.00 – 2.67; p = 0.050).
Conclusion
The results of the study suggest that severe hepatotoxicity following initiation of HAART in this cohort is low compared to other previously studied cohorts. The high incidence rate of severe hepatotoxicity in the first two months of initiating HAART necessitates the need for more frequent and careful monitoring of ALT levels early during therapy. Patients on a nevirapine-based regimen have a higher risk of developing severe hepatotoxicity when compared to their counterparts on an efavirenz-based regimen, a result consistent with findings from previous studies.

Description:

M.Sc. (Epidemiology), Faculty of Health Sciences, University of the Witwatersrand, 2011